BCR-ABL regulates death receptor expression for TNF-related apoptosis-inducing ligand (TRAIL) in Philadelphia chromosome-positive leukemia.
Allogeneic stem cell transplantation (allo-SCT) is a potentially curative therapy for chronic myeloid leukemia and Philadelphia chromosome-positive (Ph(+)) acute lymphoblastic leukemia, and the graft-vs-leukemia (GVL) effect can eradicate residual leukemia after allo-SCT. Ph(+) leukemia cells frequently express death-inducing receptors (DR4 and DR5) for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which is one of the cytotoxic ligands expressed on cytotoxic T cells and natural killer cells mediating the GVL effect. Here we demonstrate that imatinib specifically downregulated DR4 and DR5 expression in cell lines and clinical samples of Ph(+) leukemia. Second-generation tyrosine kinase inhibitors (dasatinib and nilotinib) and short hairpin RNA against bcr-abl also downregulated DR4 and DR5 expression in Ph(+) leukemia cells, and transfection of bcr-abl into a Ph(-) leukemia cell line induced DR4 and DR5 expression, which was abrogated by imatinib treatment. Accordingly, Ph(+) leukemia cells that had been pretreated with imatinib showed resistance to the pro-apoptotic activity of recombinant human soluble TRAIL. These observations demonstrate that BCR-ABL is critically involved in the leukemia-specific expression of DR4 and DR5 and in the susceptibility of Ph(+) leukemia to TRAIL-mediated anti-leukemic activity, providing new insight into the mechanisms of the tumor-specific cytotoxic activities of TRAIL.


Spatiotemporal Thermal Variations in Moroccan Cities: A Comparative Analysis.
This study examines the Land Surface Temperature (LST) trends in eight key Moroccan cities from 1990 to 2020, emphasizing the influential factors and disparities between coastal and inland areas. Geographically weighted regression (GWR), machine learning (ML) algorithms, namely XGBoost and LightGBM, and SHapley Additive exPlanations (SHAP) methods are utilized. The study observes that urban areas are often cooler due to the presence of urban heat sinks (UHSs), more noticeably in coastal cities. However, LST is seen to increase across all cities due to urbanization and the degradation of vegetation cover. The increase in LST is more pronounced in inland cities surrounded by barren landscapes. Interestingly, XGBoost frequently outperforms LightGBM in the analyses. ML models and SHAP demonstrate efficacy in deciphering urban heat dynamics despite data quality and model tuning challenges. The study's results highlight the crucial role of ongoing urbanization, topography, and the existence of water bodies and vegetation in driving LST dynamics. These findings underscore the importance of sustainable urban planning and vegetation cover in mitigating urban heat, thus having significant policy implications. Despite its contributions, this study acknowledges certain limitations, primarily the use of data from only four discrete years, thereby overlooking inter-annual, seasonal, and diurnal variations in LST dynamics.


Comparison of the effectiveness of mydriasis by two instillation methods of combined 0.75% tropicamide and 2.5% phenylephrine eye drop in preterm infants.
To compare the effectiveness and safety of two instillation methods of combined 0.75% tropicamide and 2.5% phenylephrine at 0, 5 minutes (min) with the same combined regimen at 0,30 minutes in preterm infants. A prospective, cross-over, randomized controlled trial was performed to compare 0, 5-min instillation (Method A) of combined 0.75% tropicamide and 2.5% phenylephrine with 0, 30-min instillation (Method B) of the same regimen. Forty-two preterm infants scheduled for screening retinopathy of prematurity (ROP) were randomly assigned to two groups. Group 1 was defined as preterms applied by Method A at first examination then by Method B 1-4 weeks apart whereas vice versa in Group 2. Pupil size, heart rate (HR), systolic and diastolic blood pressure (SBP, DBP) were recorded before and after eye-drop instillation. Mean time to 7-mm pupil size was no statistically significant difference between the two methods (Method A 46.47 min, Method B 46.58 min; p = 0.894). Method B has mean longer time to maintain 7-mm pupil size than Method A (Method A 67.67 min, Method B 75.33 min); but not statistically significant different (p = 0.323). HR, SBP and DBP were not significant change between the two methods. Both instillation methods produced consistently sufficient mydriasis and safety for evaluation peripheral fundus. Method B has slight longer mydriatic effect than Method A; thus giving more time to evaluate infant's eye for ophthalmologists.


[Metabolism of nicousamide in rat and human liver in vitro].
This paper is aimed to study the metabolic kinetics of nicousamide in rat liver microsomes and cytosol and to identify the major metabolite and drug metabolizing enzymes involved in the metabolism of nicousamide in rat and human liver microsomes by selective inhibitors in vitro. The concentration of nicousamide was determined by HPLC-UV method. The metabolite of nicousamide in rat and human liver microsomes was isolated and identified by LC-MS/MS. The major metabolite of nicousamide in rat and human liver microsomes was identified to be 3-(3'-carboxy-4'-hydroxy-anilino-carbo-)-6-amino-7-hydroxy-8-methyl-coumarin (M1). The metabolite of nicousamide in rat plasma, urine, bile and liver was consistent with M1. The metabolism of nicousamide can be catalyzed by several reductases, including CYP450 reductases, cytochrome b5 reductases and CYP2C6 in rat liver microsomes, as well as xanthine oxidase and DT-diaphorase in rat liver cytosol.


The origin of stability and high Co2+/3+ redox utilization for FePO4-coated LiCo0.90Ti0.05PO4/MWCNT nanocomposites for 5 V class lithium ion batteries.
Highly-dispersed 10 wt% FePO4 (FP)-coated LiCo0.90Ti0.05PO4 (LCTP) was successfully synthesized within a multiwalled carbon nanotube matrix via our original ultracentrifugation process. 10 wt% FP-coated LCTP sample showed a higher discharge capacity of 116 mA h g-1 together with stable cycle performance over 99% of capacity retention at the 100th cycle in high voltage. A combination of TEM, XRD, XPS, and XAFS analyses suggests that (i) Ti4+-substitution increases the utilization of Co redox (capacity increase) in LCP crystals by suppressing the Co3O4 formation and creating the vacancies in Co sites, and (ii) the FP-coating brought about the Fe enrichment of the surface of LCTP which prevents an irreversible crystal structure change and electrolyte decomposition during cycling, resulting in the stable cycle performance.


A research primer for studies of cognitive changes across the menopause transition.
There has been a proliferation of studies demonstrating important sex differences in cognitive aging and dementia, and with this an increased interest in the role of menopause and sex steroid hormones in women's brain health. Foundational longitudinal studies of cognitive changes from the premenopause to perimenopause stage have shown reliable declines in verbal memory, with variable findings in processing speed, attention/working memory and verbal fluency. Continued research is needed to advance understanding of the range of cognitive domains affected, the duration of cognitive changes, the generalizability of these changes across cultures, the factors that account for such changes and the factors that can improve cognition at this time. In this article, we briefly review and draw on findings from large longitudinal studies of cognitive changes across the menopause transition to inform the design of future studies on this topic. We focus on key issues such as objective versus subjective cognitive measures; cognitive domains and tests; staging menopause; study design; mediators of cognitive effects (including hormones and menopause symptoms); and consideration of key covariates. We suggest that a more uniform and evidence-based approach to the investigation of these issues can advance the quality of the science in menopause and cognition.


Perforation rates for nonsterile examination gloves in routine dermatologic procedures.
Low cost, nonsterile examination gloves are used routinely to perform various dermatologic procedures. To evaluate the perforation rate of nonsterile examination gloves in routine dermatologic procedures. Three hundred fifty nonsterile latex examination gloves used to perform shave biopsies were evaluated for perforations using an air inflation/water submersion method. Ninety gloves, which were intentionally perforated with a 30-gauge needle, were used as controls to assess our evaluation method. Eight of the 350 gloves were found to have a perforation, which corresponds to a 2.3% perforation rate. Seven of the eight perforations were found in the web space between the second and third finger sleeves, with one being an obvious manufacturing error. All 90 perforations of the control group were correctly identified. There appears to be a very low risk of glove perforation when nonsterile examination gloves are used in routine dermatologic procedures.


Assessment and Prevention of Lead Poisoning in Refugee Populations.
Lead is a neurotoxin, and there are no safe blood lead levels identified for children. Even low levels of lead in blood have been shown to permanently harm the brain, affecting a child's development, intelligence, and academic achievement. In the U.S., refugee children are at an increased risk for lead poisoning. Preventing lead exposure can reduce damage to children's health. It is imperative that clinicians conduct an exposure assessment and offer anticipatory guidance to prevent exposure to lead, especially with sources such as cosmetics, ceramics, herbs, and toys.


The promise of combining radiation therapy and immunotherapy: morbidity and toxicity.
Radiation therapy and immunotherapy in partnership may have the capability of delivering a therapeutic effect exceeding the sum of its parts. The possible relationship has been demonstrated in murine models and has been extended to a variety of clinical trials. Though the standard notion of whole body radiation therapy is immunosuppressive, there is growing evidence toward the contrary for focal radiation therapy. Furthermore, if immunotherapeutic techniques can retune the immune system against cancerous cells, they should have obvious benefits for advanced treatments moving forward. Herein, we explore the promise in combining radiation therapy and immunotherapy with distinct focus on potential morbidities and toxicities through analysis of completed clinical trials.


A Bayesian sequential design with binary outcome.
Several researchers have proposed solutions to control type I error rate in sequential designs. The use of Bayesian sequential design becomes more common; however, these designs are subject to inflation of the type I error rate. We propose a Bayesian sequential design for binary outcome using an alpha-spending function to control the overall type I error rate. Algorithms are presented for calculating critical values and power for the proposed designs. We also propose a new stopping rule for futility. Sensitivity analysis is implemented for assessing the effects of varying the parameters of the prior distribution and maximum total sample size on critical values. Alpha-spending functions are compared using power and actual sample size through simulations. Further simulations show that, when total sample size is fixed, the proposed design has greater power than the traditional Bayesian sequential design, which sets equal stopping bounds at all interim analyses. We also find that the proposed design with the new stopping for futility rule results in greater power and can stop earlier with a smaller actual sample size, compared with the traditional stopping rule for futility when all other conditions are held constant. Finally, we apply the proposed method to a real data set and compare the results with traditional designs.


Substrate uptake tests and quantitative FISH show differences in kinetic growth of bulking and non-bulking activated sludge.
The competition between filaments and floc formers in activated sludge has been historically described using kinetic selection. However, recent studies have suggested that bacterial storage may also be an important factor in microbial selection, since the dynamic nature of substrate flows into wastewater treatment plants elicit transient responses from microorganisms. Respirometry-based kinetic selection should thus be reevaluated by considering cell storage, and a more reliable method should be developed to include bacterial storage in the analysis of growth of filaments and floc formers in activated sludge. In this study, we applied substrate uptake tests combined with metabolic modeling to determine the growth rates, yields and maintenance coefficients of bulking and non-bulking activated sludge developed in lab scale reactors under feast and famine conditions. The results of quantitative fluorescence in situ hybridization (FISH) showed that the filaments Eikelboom Type 1851, Type 021N, and Thiothrix nivea were dominant in bulking sludge, comprising 42.0 % of mixed liquor volatile suspended solids (MLVSS), with 61.6% of the total filament length extending from flocs into bulk solution. Only low levels of Type 1851 filament length (4.9% of MLVSS) occurred in non-bulking sludge, 83.0% of which grew inside the flocs. The kinetic parameters determined from the substrate uptake tests were consistent with those from respirometry and showed that filamentous bulking sludge had lower growth rates and maintenance coefficients than non-bulking sludge. These results provide support for growth kinetic differences in explaining the competitive strategy of filamentous bacteria.


Treatment of chronic hepatitis C infection with cryoglobulinemia.
Mixed cryoglobulinemia is characterized by a wide spectrum of manifestations that may vary from mild symptoms (such as purpura, arthralgias, and Raynaud phenomenon) to life-threatening conditions (such as acute abdomen, hyperviscosity syndrome, and renal involvement). Hepatitis C virus infection is considered the principal trigger of the disease. Therefore, the treatment not only should be tailored to the prevailing symptom but also take into account the presence of a chronic, often smoldering infection. Symptomatic therapies are to be used in cases of minor clinical manifestations and aggressive modalities in cases of life-threatening conditions. The use of aggressive cytotoxic regimens should actually be stopped and every potentially immunosuppressive drug should be used with caution. Antiviral medications are used with growing frequency. To date, a few small trials with interferon-alpha alone or in combination with ribavirin in mixed cryoglobulinemia have been conducted. This overview deals with the current approach to the management of mixed cryoglobulinemia, focusing in particular on antiviral treatment in hepatitis C virus infection with or without mixed cryoglobulinemia.


Immunolocalization of actin in Paramecium cells.
We have selected a conserved immunogenic region from several actin genes of Paramecium, recently cloned in our laboratory, to prepare antibodies for Western blots and immunolocalization. According to cell fractionation analysis, most actin is structurebound. Immunofluorescence shows signal enriched in the cell cortex, notably around ciliary basal bodies (identified by anti-centrin antibodies), as well as around the oral cavity, at the cytoproct and in association with vacuoles (phagosomes) up to several mum in size. Subtle strands run throughout the cell body. Postembedding immunogold labeling/EM analysis shows that actin in the cell cortex emanates, together with the infraciliary lattice, from basal bodies to around trichocyst tips. Label was also enriched around vacuoles and vesicles of different size including "discoidal" vesicles that serve the formation of new phagosomes. By all methods used, we show actin in cilia. Although none of the structurally well-defined filament systems in Paramecium are exclusively formed by actin, actin does display some ordered, though not very conspicuous, arrays throughout the cell. F-actin may somehow serve vesicle trafficking and as a cytoplasmic scaffold. This is particularly supported by the postembedding/EM labeling analysis we used, which would hardly allow for any large-scale redistribution during preparation.


Nature of selection varies on different domains of IFI16-like PYHIN genes in ruminants.
ALRs (AIM2-like Receptors) are germline encoded PRRs that belong to PYHIN gene family of cytokines, which are having signature N-terminal PYD (Pyrin, PAAD or DAPIN) domain and C-terminal HIN-200 (hematopoietic, interferon-inducible nuclear protein with 200 amino acid repeat) domain joined by a linker region. The positively charged HIN-200 domain senses and binds with negatively charged phosphate groups of single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) purely through electrostatic attractions. On the other hand, PYD domain interacts homotypically with a PYD domain of other mediators to pass the signals to effector molecules downwards the pathways for inflammatory responses. There is remarkable inter-specific diversity in the numbers of functional PYHIN genes e.g. one in cow, five in human, thirteen in mice etc., while there is a unique loss of PYHIN genes in the bat genomes which was revealed by Ahn et al. (2016) by studying genomes of ten different bat species belonging to sub-orders yinpterochiroptera and yangochiroptera. The conflicts between host and pathogen interfaces are compared with "Red queen's arms race" which is also described as binding seeking dynamics and binding avoidance dynamics. As a result of this never-ending rivalry, eukaryotes developed PRRs as antiviral mechanism while viruses developed counter mechanisms to evade host immune defense. The PYHIN receptors are directly engaged with pathogenic molecules, so these should have evolved under the influence of selection pressures. In the current study, we investigated the nature of selection pressure on different domain types of IFI16-like (IFI16-L) PYHIN genes in ruminants. Three transcript variants of the IFI16-like gene were found in PBMCs of ruminant animals-water buffalo, zebu cattle, goat, and sheep. The IFI16-like gene has one N-terminal PYD domain and one C-terminal HIN-200 domain, separated by an inter-domain linker region. HIN domain and inter-domain region are positively selected while the PYD domain is under the influence of purifying selection. Herein, we conclude that the nature of selection pressure varies on different parts (PYD domain, HIN domain, and inter-domain linker region) of IFI16-like PYHIN genes in the ruminants. This data can be useful to predict the molecular determinants of pathogen interactions.


Habitual physical activity in children: the role of genes and the environment.
Understanding the factors that contribute to physical inactivity in children is important because sedentary behavior strongly relates to metabolic disorders such as obesity and diabetes. We aimed to quantify the genetic and environmental influences on physical activity energy expenditure (PAEE) in 100 sex-concordant dizygotic (n = 38) and monozygotic (n = 62) twin pairs aged 4-10 y. Resting metabolic rate (RMR) was assessed by using respiratory gas exchange, total energy expenditure (TEE) by using doubly labeled water, and body composition by using dual-energy X-ray absorptiometry. Structural equation modeling was used to partition the phenotypic variance into additive genetic (a2) and common (c2) and unshared (e2) environmental components. Because PAEE [TEE - (RMR + 0.1 x TEE)] depends on body weight, which is highly heritable, we tested several models: 1) after adjustment for age, sex, ethnicity, study date, season, and weight, a2 explained none of the phenotypic variance in PAEE (95% CI: 0%, 38%), whereas c2 and e2 accounted for 69% (33%, 77%; P = 0.001) and 31% (23%, 39%; P < 0.001) of the variance, respectively; 2) after adjustment for the cofactors in model 1, a2 explained 19% of the phenotypic variance in TEE (0%, 60%; P = 0.13), whereas c2 and e2 accounted for 59% (16%, 79%; P = 0.007) and 23% (17%, 31%; P < 0.0001) of the variance, respectively; 3) in models adjusted as above (excluding weight), a2 explained no variance in physical activity level (TEE/RMR) (0%, 32%; P = 0.50), whereas c2 and e2 explained 65% (34%, 60%; P = 0.001) and 35% (28%, 45%; P < 0.0001) of the variance, respectively. Our data suggest that the familial resemblance in physical activity in these children is explained predominantly by shared environmental factors and not by genetic variability.


Adaptation and validation of the Diabetes Management Self-Efficacy Scale to Brazilian Portuguese.
to perform the cultural adaptation and validation of the Diabetes Management Self-efficacy Scale for Patients with Type 2 Diabetes Mellitus with a Brazilian population sample. cross-sectional methodological study in which the adaptation and validation process included the stages recommended in the literature. Construct validity and reliability were assessed with 200 adults with type 2 diabetes mellitus. the items indicated by the panel of judges and by the target population were adjusted in the cultural adaptation to improve clarity and understanding. The instrument's four factors remained in the confirmatory factor analysis with factor loadings of items greater than 0.30, except for factor 4; convergent validity, verified by the multitrait-multimethod analysis, presented inter-item correlations from 0.37 to 0.92, while for discriminant validity, 100% of the items presented greater correlation in their own factors. Cronbach's coefficient alpha for the total scale was 0.78, ranging from 0.57 to 0.86 among factors. semantic, cultural, conceptual and idiomatic equivalences were achieved and the instrument's Brazilian version also presented psychometric properties that showed evidence of reliability and validity. Thus, it can be applied both in clinical practice and research. Self-efficacy is useful for planning and assessing educational interventions, as well as predicting behavior modification in self-care.


Symptom Severity and Care Delay among Patients with Serious Mental Illness.
This study investigated associations between psychiatric symptom severity and delay in seeking general medical services among individuals with serious mental illness. The association of psychiatric symptom severity, measured by the Positive and Negative Syndrome Scale (PANSS), and general medical care delay was examined among 271 patients at two urban, outpatient psychiatric clinics. Higher scores for PANSS paranoid/belligerence were associated with delays in accessing general medical care (adjusted odds ratio [AOR]=1.46, 95% confidence interval [CI]=1.04-2.01, p=.025). Higher scores on the depression symptom cluster were also associated with care delay (AOR=1.43, 95% CI=1.06-1.93, p=.018). Other symptom types showed no associations with care delay. Severity of specific psychiatric symptoms was associated with delays in seeking general medical care among people with serious mental illness. Increased focus on psychiatric symptom management may reduce medical care delay, thereby reducing the elevated morbidity and mortality among this population.


Drug resistance effects of ribosomal protein L24 overexpression in hepatocellular carcinoma HepG2 cells.
The morbidity and mortality rate of liver cancer continues to rise in China and advanced cases respond poorly to chemotherapy. Ribosomal protein L24 has been reported to be a potential therapeutic target whose depletion or acetylation inhibits polysome assembly and cell growth of cancer. Total RNA of cultured amycin-resistant and susceptible HepG2 cells was isolated, and real time quantitative RT-PCR were used to indicate differences between amycin-resistant and susceptible strains of HepG2 cells. Viability assays were used to determine amycin resistance in RPL24 transfected and control vector and null- transfected HepG2 cell lines. The ribosomal protein L24 transcription level was 7.7 times higher in the drug-resistant HepG2 cells as compared to susceptible cells on quantitative RT-PCR analysis. This was associated with enhanced drug resistance as determined by methyl tritiated thymidine (3H-TdR) incorporation. The ribosomal protein L24 gene may have effects on drug resistance mechanisms in hepatocellular carcinoma HepG2 cells.


Zinc-Air Battery-Based Desalination Device.
Efficiently storing electricity generated from renewable resources and desalinating brackish water are both critical for realizing a sustainable society. Previously reported desalination batteries need to work in alternate desalination/salination modes and also require external energy inputs during desalination. Here, we demonstrate a novel zinc-air battery-based desalination device (ZABD), which can desalinate brackish water and supply energy simultaneously. The ZABD consists of a zinc anode with a flowing ZnCl2 anolyte stream, a brackish water stream, and an air cathode with a flowing NaCl catholyte stream, separated by an anion-exchange membrane and a cation-exchange membrane, respectively. During the discharging, ions in brackish water move to the anolyte and catholyte, and they return to the feed steam during charging. The ZABD can desalt brackish water from 3000 ppm to the drinking water level at 120.1 ppm in one step and concurrently provide an energy output up to 80.1 kJ mol-1 under a discharge current density of 0.25 mA cm-2. Further, the ZABD can be charged/discharged over 20 cycles without significant performance deterioration, demonstrating its reversibility. Moreover, the desalination performances can be adjusted by varying current densities and are also influenced by the initial concentration of salt feeds. Besides, two ZABD devices were connected in series to drive 60 light-emitting diodes during the salt removal process without external power supply over 2000 min. Overall, this ZABD system demonstrates the potential for simultaneous water desalination and energy supply, which is suitable for many urgent situations.


Ceramides modulate programmed cell death in plants.
The balance between the bioactive sphingolipid ceramide and its phosphorylated derivative has been proposed to modulate the amount of programmed cell death (PCD) in eukaryotes. We characterized the first ceramide kinase (CERK) mutant in any organism. The Arabidopsis CERK mutant, called accelerated cell death 5, accumulates CERK substrates and shows enhanced disease symptoms during pathogen attack and apoptotic-like cell death dependent on defense signaling late in development. ACD5 protein shows high specificity for ceramides in vitro. Strikingly, C2 ceramide induces, whereas its phosphorylated derivative partially blocks, plant PCD, supporting a role for ceramide phosphorylation in modulating cell death in plants.


Infective endocarditis with negative blood cultures.
Culture-negative endocarditis is important as it has a relatively poor prognosis. The principal reason for negative cultures is prior antibiotic therapy although fastidious organisms such as Bartonella spp. and Coxiella burnetii are also important. PCR may offer significant advantages in diagnosis but tests require standardisation. Modification of current diagnostic criteria is required. Empirical cover of MRSA needs to be considered.


C-reactive protein independently predicts HIV-related outcomes among women and children in a resource-poor setting.
To evaluate C-reactive protein (CRP) as a predictor of HIV-related outcomes among women and children in a resource-poor setting. We measured serum CRP concentration among 606 HIV-infected women, all of whom were not taking highly-active antiretroviral therapy, 3 to 11 months after they gave birth, and assessed relationships of CRP to HIV-related endpoints, including maternal disease progression, mother-to-child transmission of HIV, and maternal and child mortality. We used Cox proportional hazards and regression models adjusted for age, sociodemographic characteristics, anthropometric measurements, hemoglobin, CD4 cell count, HIV viral load, and, for child outcomes, breastfeeding status. Ninety-four women had a high CRP concentration (> 10 mg/l). During the follow-up, 56 women progressed to WHO stage 4 and 188 died, and a high maternal CRP concentration was associated with a 2.26-fold [95% confidence interval (CI), 1.64-3.12] greater risk of progression to stage 4 or death. Among children, 174 acquired HIV and 116 died by age 2 years, and a high maternal CRP concentration was associated with a 3.03-fold (95% CI, 1.85-4.96) greater risk of child mortality. In multivariate analyses among adults, a high maternal CRP concentration was associated with a 1.55-fold (95% CI, 1.08-2.23) greater risk of progression to stage 4 or death. A maternal CRP concentration was not significantly associated with mother-to-child transmission of HIV. A high maternal CRP concentration independently predicts HIV disease progression, maternal mortality, and child mortality in a resource-poor setting. C-reactive protein may be an important and inexpensive prognostic indicator for HIV-infected women and their children.


Meta-analysis of laparoscopic vs open cholecystectomy in elderly patients.
To investigate the comparative effect of laparoscopic and open cholecystectomy in elderly patients. Laparoscopic cholecystectomy has induced a revolution in the treatment of gallbladder disease. Nevertheless, surgeons have been reluctant to implement the concepts of minimally invasive surgery in older patients. A systematic review of Medline was embarked on, up to June 2013. Studies which provided outcome data on patients aged 65 years or older, subjected to laparoscopic or open cholecystectomy were considered. Mortality, morbidity, cardiac and pulmonary complications were the outcome measures of treatment effect. The methodological quality of selected studies was appraised using valid assessment tools. Τhe random-effects model was applied to synthesize outcome data. Out of a total of 337 records, thirteen articles (2 randomized and 11 observational studies) reporting on the outcome of 101559 patients (48195 in the laparoscopic and 53364 in the open treatment group, respectively) were identified. Odds ratios (OR) were constantly in favor of laparoscopic surgery, in terms of mortality (1.0% vs 4.4%, OR = 0.24, 95%CI: 0.17-0.35, P < 0.00001), morbidity (11.5% vs 21.3%, OR = 0.44, 95%CI: 0.33-0.59, P < 0.00001), cardiac (0.6% vs 1.2%, OR = 0.55, 95%CI: 0.38-0.80, P = 0.002) and respiratory complications (2.8% vs 5.0%, OR = 0.55, 95%CI: 0.51-0.60, P < 0.00001). Critical analysis of solid study data, demonstrated a trend towards improved outcomes for the laparoscopic concept, when adjusted for age and co-morbid diseases. Further high-quality evidence is necessary to draw definite conclusions, although best-available evidence supports the selective use of laparoscopy in this patient population.


[The effect of immigration on lay analysis in the United States].
This paper investigates the effect of the immigration of European trained medical and non-medical psychoanalysts upon the development of lay-analysis in New York City. Using as a principle resource informal interviews with non-medical analysts who took part in the struggle to acquire classical training in the 1930's, 40's and early 50's in New York City, it chronicles the development of a secret, unofficial network of training and the eventual establishment of a state certified training Institute in the face of fierce opposition from organized psychiatry. It also questions the unconscious effect upon psychoanalysts practicing in such a professional atmosphere and speculates whether the concept of the conflict-free sphere of the ego did not fortuitously lend itself to denial of that question.


Calculation of a First-In-Man Dose of 7-O-Succinyl Macrolactin A Based on Allometric Scaling of Data from Mice, Rats, and Dogs.
7-O-Succinyl macrolactin A (SMA) exerts several pharmacological effects including anti-bacterial, anti-inflammation, and anti-cancer activities. Recently, SMA has been extensively evaluated as an anti-cancer drug. Thus, the objectives of the present study were to characterise the pharmacokinetics of SMA via both non-compartmental and compartmental analysis in mice, rats, and dogs, and to derive an appropriate first-in-man dose based on allometric scaling of the animal data. The time courses of plasma SMA concentrations after intravenous administration to rats and dogs were analysed retrospectively, as were data collected after intraperitoneal SMA injection in mice. Pharmacokinetic parameters were estimated via both noncompartmental and compartmental analysis, and were correlated with body weight and/or the potential maximum life-span. The clearance and distribution volume of SMA in humans were predicted, and a first-in-man dose proposed. A two-compartment model best described the time courses of SMA plasma concentrations after a saturation elimination process was applied to fit the dataset obtained from rats. Incorporation of the maximum potential life-span during allometric scaling was required to improve the estimation of human clearance. The SMA clearance and the distribution volume in the steady state, in a 70-kg adult male, were estimated to be 30.6 L/h and 19.5 L, respectively. To meet the area under the curve (AUC) required for anti-tumour activity, a dose of 100 mg (~1.5 mg/kg) was finally proposed as the first dose for a 70-kg human. Although toxicological profiles derived from non-clinical studies must be considered before any final decision is made, our work will facilitate clinical studies on SMA.


Marked hyperbilirubinemia in infectious mononucleosis. Analysis of laboratory data in seven patients.
While mild to moderate hepatic dysfunction is commonly encountered in infectious mononucleosis induced by Epstein-Barr virus (EBV), clinical jaundice with high bilirubin levels (greater than or equal to 6.0 mg/dL [greater than or equal to 103 mumol/L] is only occasionally encountered. In this study, seven patients with primary EBV infections had peak bilirubin levels of 10.2 to 23.0 mg/dL (174 to 393 mumol/L) and, for the most part, presented initial diagnostic problems. Complications included the virus-associated hemophagocytic syndrome and acute respiratory distress syndrome in one patient and transient renal failure in another. The laboratory data suggested that a combination of hemolysis and viral-induced cholestasis was responsible for the intense hyperbilirubinemia in at least five patients. Physicians should be aware that marked hyperbilirubinemia can occur with EBV-induced infectious mononucleosis and, thereby, obviate the need for costly diagnostic laboratory tests and, occasionally, invasive procedures.


Common mechanisms of drug interactions with sodium and T-type calcium channels.
Voltage-gated sodium (Na(v)) and calcium (Ca(v)) channels play important roles in physiological processes, including neuronal and cardiac pacemaker activity, vascular smooth muscle contraction, and nociception. They are thought to share a common ancestry, and, in particular, T-type calcium (T-type) channels share structural similarities with Na(v) channels, both with regard to membrane topology and with regard to gating kinetics, including rapid inactivation. We thus reasoned that certain drugs acting on Na(v) channels may also modulate the activities of T-type channels. Here we show that the specific Na(v)1.8 blocker 5-(4-chlorophenyl-N-(3,5-dimethoxyphenyl)furan-2-carboxamide (A803467) tonically blocks T-type channels in the low micromolar range. Similarly to Na(v)1.8, this compound causes a significant hyperpolarizing shift in the voltage dependence of inactivation and seems to promote a slow inactivation-like phenotype. We further hypothesized that the structural similarity between T-type and Na(v) channels may extend to structurally similar drug-binding sites. Sequence alignment revealed several highly conserved regions between T-type and Na(v) channels that corresponded to drug-binding sites known to alter voltage-dependent gating kinetics. Mutation of amino acid residues in this regions within human Ca(v)3.2 T-type channels altered A803467 blocking affinity severalfold, suggesting that these sites may be exploited for the design of mixed T-type and Na(v) channel blockers that could potentially act synergistically to normalize aberrant neuronal activity.


Identification and localization of glucagon-like peptide-1 and its receptor in rat brain.
The existence and distribution of glucagon-like peptide-1 (GLP-1) and its receptor in rat brain in relation to that of glucagon were examined. The concentration of GLP-1 immunoreactivity (GLP-1-IR), measured by a specific and sensitive RIA established in this study with anti GLP-1 serum (LMT-01), was found to be highest in the thalamus-hypothalamus, followed by the medulla oblongata. The distribution of glucagon-like immunoreactivity was similar to that of GLP-1-IR. However, appreciable glucagon immunoreactivity was detected only in the thalamus-hypothalamus. Gel filtration analysis showed the presence of GLP-1-IR of various molecular weights in the extract of thalamus-hypothalamus including that eluted at the same position as synthetic GLP-1 (1-37); moreover, HPLC analysis also confirmed the presence of GLP-1-IR, eluted at the exact position as synthetic GLP-1 (1-37). The distribution of receptors for GLP-1 corresponded with that of GLP-1-IR in the rat brain, except in the pituitary gland. The distribution of these receptors was also similar to that of glucagon receptors. The thalamus-hypothalamus, pituitary gland, and medulla oblongata were rich in GLP-1 and glucagon-binding sites. The binding affinities of GLP-1 and glucagon were in the nanomolar range [disocciation constant Kd approximately equal to 4 nM]. The presence of specific, high affinity receptors for GLP-1 was confirmed by demonstrating that GLP-1 stimulated cAMP formation in the thalamus-hypothalamus and the pituitary gland. The concentration of GLP-1 required for half-maximal stimulation of cAMP formation in these regions was about 1 nM. These results suggest that GLP-1 may be synthesized in certain parts of the brain and play a role as a neurosignal transmitter.


Uterine fibroids and risk of preterm birth by clinical subtypes: a prospective cohort study.
Fibroids are present in approximately one in ten pregnancies and are inconsistently linked with preterm birth. We sought to determine the association between fibroids and preterm birth in a prospective cohort with standardized research ultrasounds for characterizing fibroids in early pregnancy while accounting for the clinical paths that precede preterm birth. Participants who were pregnant or planning a pregnancy were recruited from communities in three states between 2000 and 2012. Members of this prospective cohort had a research ultrasound in the first trimester to establish pregnancy dating and to record detailed information about the presence, size, number, and location of fibroids. Baseline information from time of enrollment and a detailed first trimester interview contributed key information about candidate confounders. Birth outcomes, including clinical classification of type of preterm birth (preterm labor, preterm premature rupture of membranes, and medically indicated preterm birth) were cross-validated from participant report, labor and delivery records, and birth certificate data. Among 4,622 women with singleton pregnancies, 475 had at least one fibroid (10.3%) and 352 pregnancies resulted in preterm birth (7.6%). Prevalence of fibroids was similar for women with preterm and term births (10.2% vs. 10.3%). Fibroids were not associated with increased risk of preterm birth after taking into account confounding (risk ratio adjusted for race/ethnicity and maternal age, 0.88; 95% confidence interval, 0.62-1.24) nor any clinical subtype of preterm birth. No fibroid characteristic or combination of characteristics was associated with risk. If fibroids increase risk of preterm birth, the effect is substantially smaller than previous estimates. Given lack of effect in a large population of women from the general population, rather than higher risk academic tertiary populations previously most studied, we encourage a reconsideration of the clinical impression that presence of fibroids is a major risk factor for preterm birth.


Site-directed mutations in the vnd/NK-2 homeodomain. Basis of variations in structure and sequence-specific DNA binding.
Secondary structures, DNA binding properties, and thermal denaturation behavior of six site-directed mutant homeodomains encoded by the vnd/NK-2 gene from Drosophila melanogaster are described. Three single site H52R, Y54M, and T56W mutations, two double site H52R/T56W and Y54M/T56W mutations, and one triple site H52R/Y54M/T56W mutation were investigated. These positions were chosen based on their variability across homeodomains displaying differences in secondary structure and DNA binding specificity. Multidimensional NMR, electrophoretic mobility shift assays, and circular dichroism spectropolarimetry studies were carried out on recombinant 80-amino acid residue proteins containing the homeodomain. Position 56, but more importantly position 56 in combination with position 52, plays an important role in determining the length of the recognition helix. The H52R mutation alone does not affect the length of this helix but does increase the thermal stability. Introduction of site mutations at positions 52 and 56 in vnd/NK-2 does not modify their high affinity binding to the 18-base pair DNA fragment containing the vnd/NK-2 consensus binding sequence, CAAGTG. Site mutations involving position 54 (Y54M, Y54M/T56W, and H52R/Y54M/T56W) all show a decrease of 1 order of magnitude in their binding affinity. The roles in structure and sequence specificity of individual atom-atom interactions are described.


Benign retroperitoneal cysts of müllerian type: a clinicopathologic study of three cases and review of the literature.
Benign retroperitoneal cysts (RPCs) of müllerian type may present as a pelvic mass in a perimenopausal or postmenopausal woman, and thus clinically can mimic an ovarian malignancy. We report three women, aged 73, 45, and 68 years, who presented with large RPC masses ranging from 8 to 17 cm in diameter. Histologically, the cysts were lined by benign müllerian-type epithelium: serous epithelium in two patients and mucinous epithelium in one patient. A malignant component was not present in any of the cases. Preoperative diagnosis in two patients was ovarian carcinoma based on clinical and computerized tomography findings. Two patients are alive without evidence of disease 44 and 56 months following surgical excision, whereas one patient died of perioperative complications unrelated to the cystic lesion. Similar previously reported cases and their possible pathogenetic mechanisms are discussed. Although the müllerian type of RPCs behave in a benign manner, a malignant component has to be searched for. Thus, complete excision with careful histologic examination rather than drainage or marsupialization is recommended.


Aging demographic profile in municipalities in the state of Pará, Brazil.
To investigate socioeconomic and demographic differences regarding population aging in municipalities of the state of Pará, Brazil. Ecological study with secondary demographic, socioeconomic and health data from the 144 municipalities of the state of Pará, Brazil. Data were treated with segmentation analysis, the Mann-Whitney U test and logistic regression models, with a significance level of p ≤ 0.05. Segmentation analysis provided a single variable to describe aging in the municipalities of Pará and originated two clusters, the high and low aging rate ones, with 104 (72.22%) and 40 (27.78%) municipalities in each, respectively. The fitted model revealed an association between aging and per capita income (p = 0.021), vulnerability to poverty (p = 0.003), rich to poor ratio (p = 0.012) and density of people (p = 0.019). There is heterogeneity in the population aging among the municipalities of Pará, mainly regarding socioeconomic conditions and number of people living in the municipalities.


Neuroprosthetics for Auricular Muscles: Neural Networks and Clinical Aspects.
The mammalian external ear houses extrinsic and intrinsic auricular muscles. There are three extrinsic auricular muscles-the posterior, superior, and anterior auricular muscles-and six intrinsic muscles-the helicis major and minor, tragicus, anti-tragicus, transverse and oblique muscles. These muscles have been considered vestigial in humans. However, numerous therapeutic and diagnostic wearable devices are designed to monitor and alleviate the symptoms of neurological disorders, brainstem injuries, emotional states, and auditory functions, by making use of the neural networks of the auricular muscles and their locations, which are easily accessible for ergonomic wearable biomedical devices. They can also serve as a bio-controller of human neuroprosthetics. The functionality of these auricular muscles remains elusive and requires further experimentation for a more in-depth understanding of their anatomy. The aims of this review are (1) to provide a detailed account of the neural networks of the extrinsic and intrinsic auricular muscles, (2) to describe diagnostic and therapeutic functions of these muscles as demonstrated in the current literature, and (3) to outline existing and potential neuroprosthetic applications making use of the auricular muscles and their neural networks.


Ccpg1, a novel scaffold protein that regulates the activity of the Rho guanine nucleotide exchange factor Dbs.
Dbs is a Rho-specific guanine nucleotide exchange factor (RhoGEF) with in vitro exchange activity specific for RhoA and Cdc42. Like many RhoGEF family members, the in vivo exchange activity of Dbs is restricted in a cell-specific manner. Here we report the characterization of a novel scaffold protein (designated cell cycle progression protein 1 [Ccpg1]) that interacts with Dbs and modulates its in vivo exchange specificity. When coexpressed in mammalian cells, Ccpg1 binds to the Dbl homology/pleckstrin homology domain tandem motif of Dbs and inhibits its exchange activity toward RhoA, but not Cdc42. Expression of Ccpg1 correlates with the ability of Dbs to activate endogenous RhoA in cultured cells, and suppression of endogenous Ccpg1 expression potentiates Dbs exchange activity toward RhoA. The isolated Dbs binding domain of Ccpg1 is not sufficient to suppress Dbs exchange activity on RhoA, thus suggesting a regulatory interaction. Ccpg1 mediates recruitment of endogenous Src kinase into Dbs-containing complexes and interacts with the Rho family member Cdc42. Collectively, our studies suggest that Ccpg1 represents a new class of regulatory scaffold protein that can function as both an assembly platform for Rho protein signaling complexes and a regulatory protein which can restrict the substrate utilization of a promiscuous RhoGEF family member.


Unwelcome Diversions.
Encouraging technological progress the state has made on prescription monitoring is at the center of TMA's recommendations to the legislature to address doctor-shopping and opioid diversion.


Effects of deoxynivalenol (DON), zearalenone (ZEN), and related metabolites on equine peripheral blood mononuclear cells (PBMC) in vitro and background occurrence of these toxins in horses.
Both deoxynivalenol (DON), zearalenone (ZEN), and their metabolites are known to modulate immune cells in various species whereby viability and proliferation are influenced. Such effects were rarely examined in horses. Therefore, one aim of the present study was to titrate the inhibitory concentrations of DON, 3-acetyl-DON (3AcDON), de-epoxy-DON (DOM-1), ZEN, and α- and β-zearalenol (ZEL) at which viability and proliferation of equine PBMC were reduced by 50 % (IC50) and 10 % (IC10) in vitro. For evaluation of practical relevance of the in vitro findings, a further aim was to screen horses for the background occurrence of DON, ZEN, and their metabolites in systemic circulation and to relate toxin residues both to the inhibitory toxin concentrations and to hematological and clinical-chemical characteristics.The IC50 (μM) for DON, 3AcDON, β-ZEL, α-ZEL, and ZEN were determined at 3.09, 25.90, 75.44, 97.44, and 98.15 in unstimulated cells, respectively, while in proliferating cells, the corresponding IC50 values were 0.73, 6.89, 45.16, 75.96, and 82.51. Neither viability nor proliferation was influenced by DOM-1 up to a concentration of 100 μM.The in vivo screening (N = 49) revealed the occurrence of ZEN (N = 24), α-ZEL (N = 3), β-ZEL (N = 37), DON, and DOM-1 (N = 2). The detected concentrations were much lower than the corresponding IC50 while the IC10 of DON and β-ZEL for proliferating PBMC corresponded to approximately 26 and 35 ng/mL which might be relevant when contaminated diets are fed.Clinical-chemical and hematological traits were not related to mycotoxin residue levels excepting blood urea nitrogen which was positively correlated to the sum of β-ZEL, α-ZEL, and ZEN concentration. Whether this reflects simply the feeding history of the horses or renal failures giving rise to a prolonged half-life of the toxins needs to be clarified further.


Devices for ex vivo heart and lung perfusion.
The number of organs available for heart and lung transplantation is far short of the number that is needed to meet demand. Perfusion and ventilation of donor organs after procurement has led to exciting advances in the field of cardiothoracic transplantation. The clinical implications of this technology allows for techniques to evaluate the quality of an organ, active rehabilitation of organs after procurement and prior to implantation, and increased time between organ procurement and implantation. This ex-vivo perfusion technique has also been referred to in the lay press as the 'heart in a box' or 'lung in a box.' This review includes information from case reports, case series, and clinical trials on ex vivo heart and lung perfusion. The focus is on the devices, ventilation and perfusion techniques, outcomes, and application of the technology. Ex vivo perfusion of donor hearts and lungs prior to transplantation has proven to be a viable alternative to standard cold-preservation strategies. Its use has allowed for ongoing expansion of the donor pool. The biggest barriers to expansion of this technology are access, cost, and lack of evidence which clearly supports superior outcomes.


Immunocytochemical detection of progesterone receptor in breast carcinoma. Comparison of two monoclonal antibodies.
Immunocytochemical progesterone receptor (PR) assays employing two different monoclonal antireceptor antibodies (mPRi, JZB39) were compared with each other and with the dextran-coated charcoal assay (DCC) in human breast carcinoma. The immunocytochemical analyses were semiquantitatively scored (histoscore) based on relative staining intensity and the percentage of positively stained carcinoma cell nuclei. The immunocytochemically determined PR status agreed with that obtained by the DCC assay in 76% of the cases when the monoclonal antibody mPRi was used. The agreement was slightly better (82%) with the immunocytochemical assay using the JZB39 antibody. The semiquantitative histoscores correlated significantly with log-transformed cytosol PR concentrations in the DCC assay (mPRi, R = 0.543; JZB39, R = 0.618; P less than 0.0001 for both). The histoscores obtained with the mPRi and JZB39 antibodies were highly correlated with each other in adjacent frozen sections (R = 0.84, P less than 0.0001) the latter antibody giving somewhat higher histoscores. These results further validate the use of immunocytochemical PR assays for routine diagnostic purposes, especially when sufficient material is not available for DCC assays.


Introduction: A lifelong interdisciplinary approach to common arterial trunk, transposition of the great arteries, and other evolving challenges in paediatric and congenital cardiac disease.
This December issue of Cardiology in the young represents the tenth annual publication generated from the two meetings that compose "HeartWeek in Florida". "HeartWeek in Florida", the joint collaborative project sponsored by the Cardiac Center at the Children's Hospital of Philadelphia, together with All Children's Hospital of Saint Petersburg and Johns Hopkins Medicine, averages over 1000 attendees every year and is now recognized as one of the major planks of continuing medical and nursing education for those working in the fields of diagnosis and treatment of cardiac disease in the fetus, neonate, infant, child, and adult. "HeartWeek in Florida" combines the International Symposium on Congenital Heart Disease, organised by All Children's Hospital and Johns Hopkins Medicine and entering its 13th year, with the Annual Postgraduate Course in Pediatric Cardiovascular Disease, organised by The Children's Hospital of Philadelphia and entering its 17th year. The theme of this supplement generated from the 2012 HeartWeek in Florida is "A Lifelong Interdisciplinary Approach to Common Arterial Trunk, Transposition of the Great Arteries, and Other Evolving Challenges in Paediatric and Congenital Cardiac Disease". We would like to acknowledge the tremendous contributions made to medicine by Richard Jonas; and therefore, we dedicate this HeartWeek 2012 Supplement to him.


Using an auditory sensory substitution device to augment vision: evidence from eye movements.
Sensory substitution devices convert information normally associated with one sense into another sense (e.g. converting vision into sound). This is often done to compensate for an impaired sense. The present research uses a multimodal approach in which both natural vision and sound-from-vision ('soundscapes') are simultaneously presented. Although there is a systematic correspondence between what is seen and what is heard, we introduce a local discrepancy between the signals (the presence of a target object that is heard but not seen) that the participant is required to locate. In addition to behavioural responses, the participants' gaze is monitored with eye-tracking. Although the target object is only presented in the auditory channel, behavioural performance is enhanced when visual information relating to the non-target background is presented. In this instance, vision may be used to generate predictions about the soundscape that enhances the ability to detect the hidden auditory object. The eye-tracking data reveal that participants look for longer in the quadrant containing the auditory target even when they subsequently judge it to be located elsewhere. As such, eye movements generated by soundscapes reveal the knowledge of the target location that does not necessarily correspond to the actual judgment made. The results provide a proof of principle that multimodal sensory substitution may be of benefit to visually impaired people with some residual vision and, in normally sighted participants, for guiding search within complex scenes.


Outcome of nonheart-beating donor kidneys with prolonged delayed graft function after transplantation.
Nonheart-beating donor (NHBD) kidneys are frequently associated with delayed graft function (DGF), with a deleterious effect on kidney function and allograft survival. The influence and the duration of DGF on the outcome of NHBD kidneys are assessed. All recipients of an NHBD kidney in the period 1993-2003 were reviewed. Excluded from analysis were patients with primary nonfunction (PNF). One hundred and five patients with a functioning NHBD graft were reviewed: 23 (22%) had immediate function (group 1), 40 (38%) had DGF < or = 2 weeks (group 2), 31 (30%) had DGF 15 days to 4 weeks (group 3) and 11 (10%) had DGF for > 4 weeks (group 4). Creatinine clearance at 3 months was higher in groups 1 and 2 versus group 4 (p = 0.015 and p = 0.006, respectively) and was higher in group 2 versus group 4, at 1 year (p = 0.01). Graft survival was 95%, 98%, 97% and 89%, respectively, at 1 year and 95%, 85%, 77% and 89%, respectively, at 5 years, which was not significantly different. The duration of DGF in NHB kidneys has a negative effect on creatinine clearance, but no effect on graft survival.


Enhanced production and characterization of a solvent stable amylase from solvent tolerant Bacillus tequilensis RG-01: thermostable and surfactant resistant.
Ten bacterial strains isolated from the soil samples in the presence of cyclohexane were screened for amylase production. Among them, culture RG-01 was adjudged as the best amylase producer and was identified as Bacillus tequilensis from MTCC, Chandigarh. The isolate showed maximum amylase production (8100 U/mL) in the presence of starch, peptone, and Ca(2+) ions at 55°C pH 7.0 within 24 h of incubation. The enzyme was stable in the presence of n-dodecane, isooctane, n-decane, xylene, toluene, n-hexane, n-butanol, and cyclohexane, respectively. The presence of benzene, methanol, and ethanol marginally reduced the amylase stability, respectively. The enzyme was showed it 100% activity at 55°C and pH 7.0 with 119% and 127% stability at 55°C and pH 7.0, respectively. The enzyme was also stable in the presence of SDS, Tween-40, Tween-60, and Tween-80 (1%) and was found stimulatory effect, respectively. Only Triton-X-100 showed a moderate inhibitory effect (5%) on amylase activity. This isolate (Bacillus tequilensis RG-01) may be useful in several industrial applications owing to its thermotolerant and organic solvents and surfactants resistance characteristics.


Directed chaotic transport in the tokamap with mixed phase space.
On the basis of the tokamap, characteristic features of magnetic field lines and zeroth-order guiding-center particle motion in the whole body of a magnetically confined plasma, e.g., a tokamak plasma, are investigated. It is shown that the tokamap exhibits a poloidal transport that can be considered as a Hamiltonian ratchet. In a situation with partially chaotic magnetic field lines the locking of the averaged poloidal velocity occurs to a value that does not depend precisely on the initial conditions. The so-called sum rule predicts the mean velocity in agreement with the observed magnitude. Possible consequences for the onset of poloidal plasma rotation in ergodized plasmas are elucidated.


Intensive treatment of cellulite based on physiopathological principles.
Aim. The aim of this paper is to report a novel intensive therapy of gynoid lipodystrophy (cellulite) based on a new hypothesis. Methods. Were evaluated in 10 patients with ages ranging between 25 and 59 years (mean 35.6 years) grade IV cellulite identified by clinical evaluation. Before initiating treatment, perimetry was performed at 5 cm intervals along both thighs, at the gluteal fold, 5, 10, and 15 cm above the gluteal fold, at the navel, and 5 cm above the navel. The patients were submitted to a 4-hour daily treatment session that consisted of manual and mechanical lymph drainage and cervical stimulation by the Godoy & Godoy technique adapted for the treatment of cellulite. After 10 sessions over two weeks, the patients were again evaluated. The paired t-test was utilized for statistical analysis with an alpha error of 5% (P value < 0.05). A reduction was identified at all of the measurement points (paired t-test; P value < 0.0001). Results. The mean reductions varied between 4.0 and 5.7 cm at the measurement points but reductions of more than 10 cm in perimeter were achieved in some patients. Conclusion. This technique involving lymphatic system stimulation is efficacious in the treatment of cellulite.


A critical appraisal of the quality of analgosedation guidelines in critically ill patients.
The management of analgesia and sedation in critically ill patients is still a challenge due to the shortage of evidence-based treatments. The main objectives of the present study were to critically evaluate the quality of current clinical practice guidelines (CPGL) published on this matter and to identify the contrasting positions and unsolved questions. Four members of the Italian Society of Anesthesia and Intensive Care (SIAARTI) council, with an extensive background in the management of critically ill patients and practice guidelines, evaluated CPGL on sedation and analgesia in critically ill patients published from January 2006 to December 2013. Evaluation was performed in accordance with the appraisal of guidelines for research and evaluation tool (AGREE II). Five documents proposed by European and American scientific societies of critical care medicine were identified and evaluated. The CPGL published in 2013 by the American Society of Critical Care Medicine showed the highest scores in all domains of the AGREE II tool, whereas scores for CPGL published in 2006 by SIAARTI showed the lowest scores. In all documents, most recommendations on the use of drugs or non-pharmacological strategies for analgesia, sedation and delirium treatment had low evidence. This quality evaluation indicated that CPGLs published by the German Association of Scientific Medical Societies, the American College of Critical Care Medicine and the PanAmerican and Iberica Federation of the Critical Care Medicine Societies should be recommended for use. Even in guidelines with a high quality rating, numerous recommendations have moderate or low levels of evidence.


Indications for nonoperative management of ureteroceles.
Ureteroceles have traditionally been managed surgically. We report our indications and outcomes of nonoperative management of ureteroceles in a select cohort. We identified prospectively for nonoperative management 11 females and 2 males with ureteroceles associated with hydronephrosis or multicystic dysplasia (MCD). Patients presented with either a febrile urinary tract infection (3) or prenatal hydronephrosis (10). All patients were evaluated with renal and bladder ultrasound, voiding cystourethrography and mercaptoacetyltriglycine-3 furosemide renography. Two subgroups were identified, consisting of 10 duplex system upper pole ureteroceles associated with nonobstructed functional systems and 3 ureteroceles associated with a completely nonfunctional single system (2) or duplex (1) kidneys with or without MCD. Median followup was 41 months (range 13 months to 8 years). Of the 13 patients 9 required no surgical intervention. Of these 9 patients 3 had either a nonfunctional upper pole moiety (1) or MCD (2) that involuted, and 6 had good function of the upper pole segments relative to the lower pole without high grade obstruction on furosemide renography. Mean upper pole relative to lower pole differential function as determined by isotope renogram in these 6 patients was 40.8% (range 28% to 65%) and median drainage half-time was 5.3 minutes (4.5 to 19.3). On sonography, hydronephrosis improved in all 6 cases, with 5 (83%) decreasing to grade 0 (3) or I (2). Of these 6 cases of duplex system ureteroceles 5 had associated ipsilateral lower pole reflux of grade III (2) or IV (3). Reflux resolved in all cases. Surgery was necessary for progressive obstruction 1 patient and for breakthrough urinary tract infection in 3. The mean upper pole differential function in the operative group of 24.3% was lower than that of the nonoperative group. The initial median drainage half-time was 12.5 minutes (range 6.9 to 20). There was no significant difference between the nonoperative and operative groups in regard to hydronephrosis grade, reflux grade or ureterocele size. Furosemide renography can identify a select subgroup of patients with ureteroceles who are candidates for nonoperative management. Ureteroceles with nonobstructed duplex systems have better preservation of renal function and a high rate of natural resolution of hydronephrosis and reflux. Ureteroceles associated with MCD or completely nonfunctioning upper pole moieties may never require surgical management.


Sirtuin1 Maintains Actin Cytoskeleton by Deacetylation of Cortactin in Injured Podocytes.
Recent studies have highlighted the renoprotective effect of sirtuin1 (SIRT1), a deacetylase that contributes to cellular regulation. However, the pathophysiologic role of SIRT1 in podocytes remains unclear. Here, we investigated the function of SIRT1 in podocytes. We first established podocyte-specific Sirt1 knockout (SIRT1(pod-/-)) mice. We then induced glomerular disease by nephrotoxic serum injection. The increase in urinary albumin excretion and BUN and the severity of glomerular injury were all significantly greater in SIRT1(pod-/-) mice than in wild-type mice. Western blot analysis and immunofluorescence showed a significant decrease in podocyte-specific proteins in SIRT1(pod-/-) mice, and electron microscopy showed marked exacerbation of podocyte injury, including actin cytoskeleton derangement in SIRT1(pod-/-) mice compared with wild-type mice. Protamine sulfate-induced podocyte injury was also exacerbated by podocyte-specific SIRT1 deficiency. In vitro, actin cytoskeleton derangement in H2O2-treated podocytes became prominent when the cells were pretreated with SIRT1 inhibitors. Conversely, this H2O2-induced derangement was ameliorated by SIRT1 activation. Furthermore, SIRT1 activation deacetylated the actin-binding and -polymerizing protein cortactin in the nucleus and facilitated deacetylated cortactin localization in the cytoplasm. Cortactin knockdown or inhibition of the nuclear export of cortactin induced actin cytoskeleton derangement and dissociation of cortactin from F-actin, suggesting the necessity of cytoplasmic cortactin for maintenance of the actin cytoskeleton. Taken together, these findings indicate that SIRT1 protects podocytes and prevents glomerular injury by deacetylating cortactin and thereby, maintaining actin cytoskeleton integrity.


Chronic hypoxia attenuates cGMP-dependent pulmonary vasodilation.
Chronic hypoxia (CH) augments endothelium-derived nitric oxide (NO)-dependent pulmonary vasodilation; however, responses to exogenous NO are reduced following CH in female rats. We hypothesized that CH-induced attenuation of NO-dependent pulmonary vasodilation is mediated by downregulation of vascular smooth muscle (VSM) soluble guanylyl cyclase (sGC) expression and/or activity, increased cGMP degradation by phosphodiesterase type 5 (PDE5), or decreased VSM sensitivity to cGMP. Experiments demonstrated attenuated vasodilatory responsiveness to the NO donors S-nitroso-N-acetylpenicillamine and spermine NONOate and to arterial boluses of dissolved NO solutions in isolated, saline-perfused lungs from CH vs. normoxic female rats. In additional experiments, the sGC inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, blocked vasodilation to NO donors in lungs from each group. However, CH was not associated with decreased pulmonary sGC expression or activity as assessed by Western blotting and cGMP radioimmunoassay, respectively. Consistent with our hypothesis, the selective PDE5 inhibitors dipyridamole and T-1032 augmented NO-dependent reactivity in lungs from CH rats, while having little effect in lungs from normoxic rats. However, the attenuated vasodilatory response to NO in CH lungs persisted after PDE5 inhibition. Furthermore, CH similarly inhibited vasodilatory responses to 8-bromoguanosine 3'5'-cyclic monophosphate. We conclude that attenuated NO-dependent pulmonary vasodilation after CH is not likely mediated by decreased sGC expression, but rather by increased cGMP degradation by PDE5 and decreased pulmonary VSM reactivity to cGMP.


IRFEL Selective Irradiation of Amorphous Solid Water: from Dangling to Bulk Modes.
Amorphous solid water (ASW) is one of the most widely studied solid phase systems. A better understanding of the nature of inter- and intramolecular forces in ASW is, however, still required to correctly interpret the catalytic role of ASW in the formation and preservation of molecular species in environments such as the icy surfaces of Solar System objects, on interstellar icy dust grains, and potentially even in the upper layers of the Earth's atmosphere. In this work, we have systematically exposed porous ASW (pASW) to mid-infrared radiation generated by a free-electron laser at the HFML-FELIX facility in The Netherlands to study the effect of vibrational energy injection into the surface and bulk modes of pASW. During multiple sequential irradiations on the same ice spot, we observed selective effects both at the surface and in the bulk of the ice. Although the density of states in pASW should allow for a fast vibrational relaxation through the H-bonded network, part of the injected energy is converted into structural ice changes as illustrated by the observation of spectral modifications when performing Fourier transform infrared spectroscopy in reflection-absorption mode. Future studies will include the quantification of such effects by systematically investigating ice thickness, ice morphology, and ice composition.


Cancer of the endometrium---a multiparametric study.
Haematological and immunological studies were performed on 36 patients with carcinoma of the endometrium prior to treatment. Haematological and coagulation studies, excluding fibrinogen, showed only minimal abnormality. However, tests for acute phase reactant proteins were abnormal in the majority of patients. There was a reduction in T cells in 31% of patients and a reduction in stimulation with PHA and PWM in 84 and 42% of patients, respectively. Autoantibodies to normal tissue antigens were present in half the patients and immune complexes were increased in 45% of patients. Carcinoembryonic antigen and B(2)-microglobulin were increased in 27 and 47% of patients respectively. Although specific tests for endometrial cancer are not yet available, a profile of tests might be of value in the diagnosis and follow-up of patients with the condition.


Agreement of Bioreactance Cardiac Output Monitoring With Thermodilution in Healthy Standing Horses.
Bioreactance is the continuous analysis of transthoracic voltage variation in response to an applied high frequency transthoracic current and was recently introduced for non-invasive cardiac output measurement (NICOM). We evaluated NICOM compared to thermodilution (TD) in adult horses. Six healthy horses were used for this prospective, blinded, experimental study. Cardiac output (CO) measurements were performed simultaneously using TD and the bioreactance method. Different cardiac output scenarios were established using xylazine (0.5 mg/kg IV) and dobutamine (1.5-3 mcg/kg/min). Statistical analysis was performed by calculating the concordance rate, performing a regression analysis, Pearson correlation, and Bland Altman. The TD-based CO and NICOM values were highly correlated for low, normal and high CO values with an overall correlation coefficient. A 4-quadrant plot showed an 89% rate of concordance. The linear regression calculated a relationship between NICOM and TDCO of Y = 0.4874 · X + 0.5936. For the corrected Bland Altman agreement, the mean bias and lower/upper limits of agreement were -0.26 and -3.88 to 3.41 L/min, respectively. Compared to TD, bioreactance- based NICOM showed good accuracy at induced low, normal, and high CO states in normal horses. Future studies performed under more clinical conditions will show if this monitor can help to assess hemodynamic status and guide therapy in horses in ICU settings and under general anesthesia.


Quantitative and textural analysis of magnetization transfer and diffusion images in the early detection of brain metastases.
The sensitivity of the magnetization transfer ratio (MTR) and apparent diffusion coefficient (ADC) for early detection of brain metastases was investigated in mice and humans. Mice underwent MRI twice weekly for up to 31 d following intracardiac injection of the brain-homing breast cancer cell line MDA-MB231-BR. Patients with small cell lung cancer underwent quarterly MRI for 1 year. MTR and ADC were measured in regions of metastasis and matched contralateral tissue at the final time point and in registered regions at earlier time points. Texture analysis and linear discriminant analysis were performed to detect metastasis-containing slices. Compared with contralateral tissue, mouse metastases had significantly lower MTR and higher ADC at the final time point. Some lesions were visible at earlier time points on the MTR and ADC maps: 24% of these were not visible on corresponding T2 -weighted images. Texture analysis using the MTR maps showed 100% specificity and 98% sensitivity for metastasis at the final time point, with 77% sensitivity 2-4 d earlier and 46% 5-8 d earlier. Only 2 of 16 patients developed metastases, and their penultimate scans were normal. Some brain metastases may be detected earlier on MTR than conventional T2 ; however, the small gain is unlikely to justify "predictive" MRI. Magn Reson Med 77:1987-1995, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.


The crystal structure of methane B at 8 GPa--an α-Mn arrangement of molecules.
From a combination of powder and single-crystal synchrotron x-ray diffraction data we have determined the carbon substructure of phase B of methane at a pressure of ∼8 GPa. We find this substructure to be cubic with space group I4¯3m and 58 molecules in the unit cell. The unit cell has a lattice parameter a = 11.911(1) Å at 8.3(2) GPa, which is a factor of √2 larger than had previously been proposed by Umemoto et al. [J. Phys.: Condens. Matter 14, 10675 (2002)]. The substructure as now solved is not related to any close-packed arrangement, contrary to previous proposals. Surprisingly, the arrangement of the carbon atoms is isostructural with that of α-manganese at ambient conditions.


A fatal case of infective endocarditis caused by an unusual suspect: Serratia marcescens.
Serratia marcescens has been reported to cause infective endocarditis among intravenous drug users, but it is extremely rare in non-intravenous drug users in Japan. In this article, we report an 85-year-old woman with diabetes mellitus who presented with low-grade fever and general fatigue. She was administered intravenous prednisolone under a diagnosis of right Bell's palsy before this admission. Blood cultures revealed positive Serratia marcescens, which was complicated by multiple cerebral infarctions after admission. Transthoracic echocardiography on day 5 revealed vegetation on the mitral valve, which was diagnosed as infective endocarditis. An operation could not be performed because of the presence of multiple cerebral infarctions. She died on day 65 because of uncontrolled heart failure.


Aerobic exercise in adult neuromuscular rehabilitation: A survey of healthcare professionals.
To evaluate the current application of aerobic exercise in adult neuromuscular rehabilitation. Cross-sectional survey. Dutch rehabilitation specialists and physical therapists in specialized centres for slowly progressive neuromuscular diseases and in primary care. Participants received a self-designed, web-based, questionnaire, including 27 close-ended questions covering 4 categories: respondent profile, application of aerobic exercise, barri-ers to prescribing aerobic exercise, and need for support to improve the application of aerobic exercise. All respondents (n = 52) prescribed aerobic exercise and in a wide variety of neuromuscular diseases, mostly applying sessions of more than 20 min, 2 days per week, over a period of 9-16 weeks, using different exercise modes and methods to target intensity. The majo-rity (81%) agreed that aerobic exercise should be incorporated into neuromuscular rehabilitation. However, all respon-dents perceived barriers to the application of aerobic exercise in one or more domains, and 77% of the respondents indicated needing support to improve application of this type of training, mostly with respect to screening procedures (54%) and dosing of exercise programmes (48%). Aerobic exercise is widely applied, yet our results raise awareness of the necessity of more evidence based knowledge, in order to develop and implement guidelines in adult neuromuscular rehabilitation.


Novel reassortant highly pathogenic avian influenza (H5N5) viruses in domestic ducks, China.
In China, domestic ducks and wild birds often share the same water, in which influenza viruses replicate preferentially. Isolation of 2 novel reassortant highly pathogenic avian influenza (H5N5) viruses from apparently healthy domestic ducks highlights the role of these ducks as reassortment vessels. Such new subtypes of influenza viruses may pose a pandemic threat.


The relation between early mother-infant skin-to-skin contact and later maternal sensitivity in South African mothers of low birth weight infants.
The relation between early mother-infant skin-to-skin contact (SSC) and mothers' subsequent sensitivity to their low birth weight infants was investigated in a study of 12 mother-infant dyads who participated in a South African randomized control study of early SSC. The dyads were visited in the home when infants were under 1 year. Amounts of SSC were taken from hospital records and home interviews. Videotapes of mother-infant interactions in the home were scored for maternal sensitivity on the Maternal Behavior Q-Sort (D.R. Pederson, G. Moran, & S. Bento, 1999) and the Maternal Behavior subscale of the Nursing Child Assessment Teaching Scale (G. Sumner & A. Spietz, 1994). Amount of SSC in infants' first 24 hr correlated with amount of SSC through the first month. Amount of SSC in infants' first 24 hr independently accounted for maternal sensitivity on both measures, indicating that early mother-infant SSC predicted subsequent maternal sensitivity.


Nanometer-sized domains in Langmuir-Blodgett films for patterning SiO2.
In this study, we prepared Langmuir-Blodgett films with domains ranging from 20 to 100 nm in size by using perfluorinated fatty acids. The domain size of the obtained LB films is markedly smaller than the ordinary domain size of hydrocarbons and fluorocarbons on the micrometer scale. The domains were prepared by controlling their growth through the addition of 2-propanol to the subphase of Langmuir monolayers. Furthermore, the prepared domains in the LB films were used as templates for patterning SiO(2) films. The obtained SiO(2) films have completely negative structures compared with those of the domains in the LB films.


Shear bond strength of different retainer wires and bonding adhesives in consideration of the pretreatment process.
We aimed to compare the shear bond strength (SBS) of three different retainer wires and three different bonding adhesives in consideration of the pretreatment process of enamel surface sandblasting. 400 extracted bovine incisors were divided into 10 groups of 20 paired specimens each. 10 specimens of each group were pretreated by enamel sandblasting. The retainer wires Bond-A-Braid™, GAC-Wildcat®-Twistflex and everStick®ORTHO were bonded to the teeth with the adhesives Transbond™-LR, Tetric-EvoFlow™ and Stick®FLOW and then debonded measuring the SBS. While sandblasting generally increased SBS for all tested combinations, the retainer wires bonded with Transbond™-LR showed the highest SBS both with and without prior sandblasting. Significantly lower SBS were found for Tetric-EvoFlow™ that were comparable to those for everStick®ORTHO. Pretreatment of enamel surfaces by sandblasting increased the SBS of all retainer-wires. Transbond™-LR showed the best results compared to Tetric-EvoFlow™ and everStick®ORTHO, while all combinations used provided sufficient bonding strengths for clinical use.


Deep learning models for cancer stem cell detection: a brief review.
Cancer stem cells (CSCs), also known as tumor-initiating cells (TICs), are a subset of tumor cells that persist within tumors as a distinct population. They drive tumor initiation, relapse, and metastasis through self-renewal and differentiation into multiple cell types, similar to typical stem cell processes. Despite their importance, the morphological features of CSCs have been poorly understood. Recent advances in artificial intelligence (AI) technology have provided automated recognition of biological images of various stem cells, including CSCs, leading to a surge in deep learning research in this field. This mini-review explores the emerging trend of deep learning research in the field of CSCs. It introduces diverse convolutional neural network (CNN)-based deep learning models for stem cell research and discusses the application of deep learning for CSC research. Finally, it provides perspectives and limitations in the field of deep learning-based stem cell research.


Culture and tension during an international space station simulation: results from SFINCSS '99.
This paper addresses the impact of cultural heterogeneity on interpersonal tension during multinational space missions. Data were collected during SFINCSS '99, which simulated the living conditions on ISS. Three crews (n = 12) were confined in connected hyperbaric chambers. Group 1 was confined for 240 d, while Groups 2 and 3 were confined for 110 d. Group 1 was composed of four Russian subjects; Group 2 included three Russian subjects and one non-Russian subject; and Group 3 included Japanese, Russian, Austrian and Canadian subjects. Group 3 included the only female participant. Peer ratings, questionnaires and interviews assessed tension within and between crews, critical incidents and cultural factors impacting on crew interaction. Compared with Group 1, Group 3 evaluated their own group and the Mission Control more negatively. A conflict between Group 1 and 3 was reflected in mutual negative ratings after 1 mo. This situation resulted in an unplanned closure of the hatch between the chambers and in one subject leaving the study prematurely. Group 3 expressed dissatisfaction with mission support and interventions from outside personnel to resolve the interpersonal problems. The entrance of an international visiting crew was reported to alleviate tension between Groups 1 and 3. Language problems and different attitudes toward gender relations were factors identified as having a major impact on the inter-group relationship. The results may demonstrate some of the difficulties faced by crewmembers belonging to cultural minorities when operational control is in the hands of one national organization, as well as the need for countermeasures designed to address these problems.


Work Engagement of Employees in Moonlighting: A Moderated Mediation Model From a Boundaryless Career Perspective.
Using a panel of 324 Chinese employees in public sectors, this paper examines the work engagement of employees in moonlighting with the proxy of boundaryless career orientations. We divided work engagement into job engagement and organizational engagement and test their relation to boundaryless career orientations. The results demonstrate that boundaryless career orientations are positively related to job engagement via the mediating effects of role conflicts, and negatively related to organizational engagement through the mediating effects of the relational psychological contracts. Moreover, organizational climate for openness moderates the negative correlation between boundaryless career orientations and role conflicts. There is no significant evidence provided for a moderating effect of organizational climate for openness between boundaryless career orientations and relational psychological contracts.


History and development of cesarean operation.
The history of cesarean birth has developed in spite of myths, physician differences, and early patient deaths and morbidity. The methods used today prevent maternal deaths and morbidity, and the cesarean operation is one of most common surgical procedures.


Evolutionary rewiring of bacterial regulatory networks.
Bacteria have evolved complex regulatory networks that enable integration of multiple intracellular and extracellular signals to coordinate responses to environmental changes. However, our knowledge of how regulatory systems function and evolve is still relatively limited. There is often extensive homology between components of different networks, due to past cycles of gene duplication, divergence, and horizontal gene transfer, raising the possibility of cross-talk or redundancy. Consequently, evolutionary resilience is built into gene networks - homology between regulators can potentially allow rapid rescue of lost regulatory function across distant regions of the genome. In our recent study [Taylor, et al. Science (2015), 347(6225)] we find that mutations that facilitate cross-talk between pathways can contribute to gene network evolution, but that such mutations come with severe pleiotropic costs. Arising from this work are a number of questions surrounding how this phenomenon occurs.


Pre-empting Antibody-Mediated Rejection: A Program of DSA Monitoring and Treatment Can Effectively Prevent Antibody Mediated Rejection.
Antibody-mediated rejection (AMR) remains a problem without a reliable treatment in the care of kidney transplant patients. We proposed and tested a program of screening for donor specific antibodies (DSA) to initiate treatment of patients before AMR was detected and to prevent its occurrence. Starting in April 2012, we stratified patients into high-, medium-, and low-risk groups for the development of DSA and instituted a program of screening for and treatment of these antibodies. We used a historic control group of patients transplanted at our center as a comparator and looked at rates of DSA testing and development as well as rates of development of AMR, cell-mediated rejection, and graft loss. 614 patients were transplanted under the protocol compared with 266 patients in the control group. Length of follow-up was similar in both groups. The group undergoing DSA screening had lower rates of DSA development (17.6% versus 24.8%, p=0.016) and that DSA was found at a significantly earlier time post-transplant (147 versus 248 days, p=0.02). Incidence of AMR was dramatically lower in the screened group (1.3% versus 8.6%, p<0.0001) with no grafts lost due to AMR. AMR was found to occur at an average of 181 days post-transplant. Rates of acute cellular rejection did not decrease in a manner similar to AMR rates. In conclusion, a program of universal risk-stratified DSA testing in kidney transplant patients can dramatically reduce rates of AMR and virtually eliminate graft loss due to AMR.


Searching for stable Si(n)C(n) clusters: combination of stochastic potential surface search and pseudopotential plane-wave Car-Parinello simulated annealing simulations.
To find low energy Si(n)C(n) structures out of hundreds to thousands of isomers we have developed a general method to search for stable isomeric structures that combines Stochastic Potential Surface Search and Pseudopotential Plane-Wave Density Functional Theory Car-Parinello Molecular Dynamics simulated annealing (PSPW-CPMD-SA). We enhanced the Sunders stochastic search method to generate random cluster structures used as seed structures for PSPW-CPMD-SA simulations. This method ensures that each SA simulation samples a different potential surface region to find the regional minimum structure. By iterations of this automated, parallel process on a high performance computer we located hundreds to more than a thousand stable isomers for each Si(n)C(n) cluster. Among these, five to 10 of the lowest energy isomers were further optimized using B3LYP/cc-pVTZ method. We applied this method to Si(n)C(n) (n = 4-12) clusters and found the lowest energy structures, most not previously reported. By analyzing the bonding patterns of low energy structures of each Si(n)C(n) cluster, we observed that carbon segregations tend to form condensed conjugated rings while Si connects to unsaturated bonds at the periphery of the carbon segregation as single atoms or clusters when n is small and when n is large a silicon network spans over the carbon segregation region.


Influence of groundwater composition on subsurface iron and arsenic removal.
Subsurface arsenic and iron removal (SAR/SIR) is a novel technology to remove arsenic, iron and other groundwater components by using the subsoil. This research project investigated the influence of the groundwater composition on subsurface treatment. In anoxic sand column experiments, with synthetic groundwater and virgin sand, it was found that several dissolved substances in groundwater compete for adsorption sites with arsenic and iron. The presence of 0.01 mmol L(-1) phosphate, 0.2 mmol L(-1) silicate, and 1 mmol L(-1) nitrate greatly reduced the efficiency of SAR, illustrating the vulnerability of this technology in diverse geochemical settings. SIR was not as sensitive to other inorganic groundwater compounds, though iron retardation was limited by 1.2 mmol L(-1) calcium and 0.06 mmol L(-1) manganese.


Adsorption and Photodegradation of Lanasol Yellow 4G in Aqueous Solution by Natural Zeolite Treated by CO2-Laser Radiation.
Natural zeolite is a widely used material with excellent environmental cleaning performance, especially in water and wastewater treatment. Natural zeolite (Zini) calcined by CO2-laser radiation (ZL) was tested as a catalyst for the photodegradation and the adsorption of industrial azo dye Lanasol Yellow 4G (LY4G) in water. Morphology, chemical structure, and surface composition of Zini and ZL were analyzed by XRD, SEM, EDS, and XPS. UV/Visible spectrophotometry was used to evaluate the photocatalytic activity of Zini and ZL. The photocatalytic activity of the studied zeolites was associated with the presence of Fe oxides in their composition. Laser-treated natural zeolite showed higher efficiency as a photocatalyst compared to untreated natural zeolite.


India and its pluralistic health system - a new philosophy for Universal Health Coverage.
In this article we attempt to put forth insights into using traditional medicine (TM) systems to achieve Universal Health Coverage (UHC). We discuss the need for reimagining India's health system and the importance of an inclusive approach for UHC. We comprehend the challenges with appropriate use of TM systems and the lessons from international experience of integrating TM systems. We highlight the pathways for better utilization of TM systems for UHC in India.


[Effects of extract of Ginkgo biloba on magnetic resonance imaging and electroencephalography in patients with delayed encephalopathy after acute carbon monoxide poisoning].
Objective: To observe the effects of extract of Ginkgo biloba (Ginaton) on magnetic resonance imaging (MRI) and electroencephalography (EEG) in patients with delayed encephalopathy after acute carbon monoxide poisoning. Methods: The 84 patients with delayed encephalopathy after acute carbon monoxide poisoning treated in our hospital from Jan. 2011 to Apr. 2016 were randomly divied into therapy group and observation group. The therapy group received routine treatments of hyperbaric oxygen, cure cerebral edema and promote brain cell metabolism, and observation group was given intravenous injection (intravenous drip) Ginaton 70 mg (adding 0.9% sodium chloride injection 250 ml) , once a day, 2 weeks for one therapeutic course. The changes of MRI and EEG before and after treatment between therapy group and observation group were observed. Results: In the observation group, the white matter and globus pallidus lesions of 14 d after treatment were smaller than those in the treatment group, and the abnormal signal intensity was decreased. At 14 days after treatment the improvement of EEG in observation group were better than therapy group (P<0.05) . Conclusion: Early treatment of extract of Ginkgo biloba (Ginaton) in delayed encephalopathy after acute carbon monoxide poisoning can effectively improve lesion and signal on MRI and abnormal rate on EEG. It has a certain therapeutic effect in clinical.


The possible role of heat shock protein-70 induction in collagen-induced arthritis in rats.
This study aimed to evaluate the possible role of heat shock protein-70 (HSP70) induction by 17-allylaminodemethoxygeldanamycin (17-AAG) in collagen-induced arthritis in rats. Male Wistar rats were divided into five groups (n = 10/group) and were treated intraperitoneally twice a week for 4 weeks, namely normal control (saline), arthritis control (AR; saline), AR + 17-AAG, AR + methotrexate (MTX), and AR + 17-AAG + MTX. At the end of the treatments, arthritic score was determined and then the animals were sacrificed. Erythrocyte sedimentation rate (ESR), serum levels of HSP70, interleukin-17 (IL-17), tumor necrosis factor-alpha (TNF-α), rheumatic factor (RF), C-reactive protein (CRP), malondialdehyde (MDA), glutathione peroxidase (GPx), and matrix metalloproteinase-9 (MMP-9) were determined. In the AR group, all parameters increased significantly, except for GPx, which showed a pronounced decrease. The 17-AAG and/or MTX treatments significantly reduced arthritic score, ESR, IL-17, TNF-α, RF, CRP, MDA, and MMP-9 with significant increase in GPx compared to the AR group. The HSP70 level was significantly higher in the AR + 17-AAG and the AR + 17-AAG + MTX groups but significantly lower in the AR + MTX group as compared to the AR group. Also, it was significantly lower in the AR + MTX group as compared to the AR + 17-AAG group. We concluded that HSP70 induction by 17-AAG attenuated the inflammatory process in a rheumatoid arthritis (RA) model induced by collagen, which suggested that HSP70 inducers can be promising agents in the treatment of RA.


Malignancies of the eyelid: a review of primary and metastatic cancers.
The eyelid can be the site of various malignant tumors, including epithelial, mesenchymal, lymphoproliferative, and endocrine neoplasms, all of which can present in unusual ways or mimic benign processes, often requiring biopsy for a definitive diagnosis. This review article presents a broad overview of some of the malignancies that have been reported to occur in eyelids, addressing clinical presentation and natural history, histologic and immunostaining characteristics, and genetic associations where relevant. The unique combination of functional importance, to protect and lubricate the eye, and cosmetic importance make management of eyelid lesions difficult. We describe a few of the diagnostic and treatment options that can be considered.


Interruption of cardiopulmonary resuscitation with the use of the automated external defibrillator in out-of-hospital cardiac arrest.
The protocol for the use of the automated external defibrillator calls for a period of "hands-off" time, during which no cardiopulmonary resuscitation (CPR) can be performed. We assessed the actual interruption time of CPR during the use of the automated external defibrillator in patients in out-of-hospital cardiac arrest. This study included 184 patients experiencing out-of-hospital cardiac arrest in which an automated external defibrillator was applied by first responders. ECG and voice recordings from the automated external defibrillator were downloaded and analyzed. Start and end times of CPR were recorded, as were intervals measured from the recordings concerning the programmed interruption time and the interruption time related to performance. The automated external defibrillators were connected for a median time of 4 minutes 47 seconds (range 31 to 1,404 seconds). CPR was performed during 45%+/-15% (mean+/-SD) of the connected time or until return of spontaneous circulation. During the automated external defibrillator connection time in the 96 patients with a shockable rhythm, CPR was performed 36%+/-20% of the time. Programmed interruption of CPR took 40%+/-15% of the automated external defibrillator connection time, and no CPR was performed related to performance during 23%+/-15% of the time. A palpable pulse was never present immediately after a shock, and return of spontaneous circulation was observed in 3 of 184 patients before arrival of the ambulance. Ultimately, return of spontaneous circulation occurred in 87 of 184 patients. First responders using automated external defibrillator voice prompts provide CPR less than half the time that the automated external defibrillator is connected to the patient. Technical improvements in automated external defibrillator rhythm analysis, more efficient resuscitation algorithms, and first-responder education could increase CPR delivery and, perhaps, improve outcome.


Traumatic lateral displacement of the scapula: a radiographic sign of neurovascular disruption.
Scapulothoracic dissociation, as manifested by lateral displacement of the scapula and acromioclavicular separation, is a previously unreported injury in which there is a complete disruption of the scapulothoracic articulation without an overlying partial or complete amputation through the soft tissue. Associated with the disruption of the scapulothoracic articulation are injuries to the brachial plexus and the subclavian artery and vein; multiple open and closed fractures of the ipsilateral upper extremity are often present also. In the patient with severe multiple injuries, scapulothoracic dissociation may not be recognized immediately, with potentially fatal consequences. In this paper we present the cases of three patients with radiographic and pathological evidence of scapulothoracic dissociation and review the literature on related injuries.


Troponin I serines 43/45 and regulation of cardiac myofilament function.
We studied Ca(2+) dependence of tension and actomyosin ATPase rate in detergent extracted fiber bundles isolated from transgenic mice (TG), in which cardiac troponin I (cTnI) serines 43 and 45 were mutated to alanines (cTnI S43A/S45A). Basal phosphorylation levels of cTnI were lower in TG than in wild-type (WT) mice, but phosphorylation of cardiac troponin T was increased. Compared with WT, TG fiber bundles showed a 13% decrease in maximum tension and a 20% increase in maximum MgATPase activity, yielding an increase in tension cost. Protein kinase C (PKC) activation with endothelin (ET) or phenylephrine plus propranolol (PP) before detergent extraction induced a decrease in maximum tension and MgATPase activity in WT fibers, whereas ET or PP increased maximum tension and stiffness in TG fibers. TG MgATPase activity was unchanged by ET but increased by PP. Measurement of protein phosphorylation revealed differential effects of agonists between WT and TG myofilaments and within the TG myofilaments. Our results demonstrate the importance of PKC-mediated phosphorylation of cTnI S43/S45 in the control of myofilament activation and cross-bridge cycling rate.